Studies of variability in the PTEN gene among Danish caucasian patients with Type II diabetes mellitus

Aim/hypothesis. Phosphatase and tensin homologue deleted from chromosome te n (PTEN) has recently been characterized as a novel member in the expanding network of proteins regulating the intracellular effects of insulin. By de phosphorylation of phosphatidyl-inositol-(3, 4, 5)-trisphosphate (PIP3) the PTEN protein regulates the insulin-dependent phosphoinositide 3-kinase (PI 3K) signalling cassette and accordingly might function as a regulator of in sulin sensitivity in skeletal muscle and adipose tissue. In this study we t ested PTEN as a candidate gene for insulin resistance and late-onset Type I I (non-insulin-dependent) diabetes mellitus in a Danish Caucasian populatio n. Methods. The nine exons of the PTEN, including intronic flanking regions we re analysed by PCR-SSCP and heteroduplex analysis in 62 patients with insul in-resistant Type II diabetes. Results. No mutations predicted to influence the expression or biological f unction of the PTEN protein but four intronic polymorphisms were identified : IVS1-96 A-->G (allelic frequency 0.22, 95% CI: 0.12-0.32), IVS3+99 C-->T (0.01, CI: 0-0.03), IVS7-3 TT-->T (0.10, CI: 0.03-0.18) and IVS8 + 32 G-->T (0.35, CI: 0.23-0.47). The IVS8 + 32 G-->T polymorphism was used as a bi-a llelic marker for the PTEN locus and examined in 379 patients with Type II diabetes and in 224 control subjects with normal glucose tolerance. The IVS 8+32 G-->T polymorphism in the PTEN was not associated with Type II diabete s and it did not have any effect on body-mass index, blood pressure, HOMA i nsulin resistance index, or concentrations of plasma glucose, serum insulin or serum C peptide obtained during an oral glucose tolerance test (OGTT). Conlusion/interpretation. Variability in the PTEN is not a common cause of Type II diabetes in the Danish Caucasian population.